Bronson M E, Lin Y P, Burchett K, Picker M J, Dykstra L A
Department of Psychology, University of North Carolina, Chapel Hill.
Psychopharmacology (Berl). 1993;111(1):69-77. doi: 10.1007/BF02257409.
The purpose of the present study was to examine the role of serotonin (5HT) in the discriminative stimulus effects of kappa opioids. Pigeons were trained to discriminate 5.6 mg/kg of the kappa opioid, U50,488, from water. During substitution tests, both U50,488 and another kappa opioid, spiradoline, produced > 80% responding on the U50,488-appropriate key. In contrast, the non-opioid compound, phencyclidine and several serotonergic compounds failed to substitute for the U50,488 discriminative stimulus across a wide range of doses. During combination tests, the selective 5HT1A agonist, 8-OH-DPAT (0.001-3.2 mg/kg), dose-dependently attenuated the discriminative stimulus effects of 5.6 mg/kg U50,488 and 3.2 mg/kg spiradoline. This effect was reversed by the 5HT1A antagonist, NAN-190 (0.01-1 mg/kg), in a dose-dependent manner. Buspirone (0.01-10 mg/kg), a 5HT1A partial agonist, also attenuated the discriminative stimulus effects of the training dose of U50,488 but ipsapirone, another 5HT1A partial agonist, did not. Ketanserin, a 5HT2 antagonist, and MDL72222, a 5HT3 antagonist, attenuated the effects of U50,488, whereas the 5HT1B,1C agonist, mCPP, and the 5HT2 agonist, DOI, did not. Depletion of 5HT with p-CPA also attenuated U50,488's discriminative stimulus effects. Taken together, the results suggest that serotonin release is an important component in the discriminative stimulus effects produced by kappa opioids; however, the effects of DOI and mCPP alone suggest that activation of post-synaptic 5HT receptors is not sufficient to produce the full spectrum of kappa opioid discriminative stimulus effects.
本研究的目的是考察血清素（5-羟色胺，5HT）在κ阿片样物质辨别刺激效应中的作用。训练鸽子区分5.6毫克/千克的κ阿片样物质U50,488和水。在替代试验中，U50,488和另一种κ阿片样物质spiradoline在与U50,488相应的按键上产生了>80%的反应。相比之下，非阿片类化合物苯环己哌啶和几种血清素能化合物在很宽的剂量范围内都不能替代U50,488的辨别刺激。在联合试验中，选择性5HT1A激动剂8-羟基二丙胺基四氢萘（8-OH-DPAT，0.001 - 3.2毫克/千克）剂量依赖性地减弱了5.6毫克/千克U50,488和3.2毫克/千克spiradoline的辨别刺激效应。5HT1A拮抗剂NAN-190（0.01 - 1毫克/千克）以剂量依赖性方式逆转了这种效应。5HT1A部分激动剂丁螺环酮（0.01 - 10毫克/千克）也减弱了训练剂量U50,488的辨别刺激效应，但另一种5HT1A部分激动剂伊沙匹隆却没有。5HT2拮抗剂酮色林和5HT3拮抗剂MDL72222减弱了U50,488的效应，而5HT1B,1C激动剂间氯苯哌嗪（mCPP）和5HT2激动剂DOI则没有。用对氯苯丙氨酸（p-CPA）耗尽5HT也减弱了U50,488的辨别刺激效应。综上所述，结果表明血清素释放是κ阿片样物质产生辨别刺激效应的一个重要组成部分；然而，单独使用DOI和mCPP的效应表明，突触后5HT受体的激活不足以产生κ阿片样物质辨别刺激效应的全谱。
